The CXCR4 antagonist plerixafor is a potential therapy for myelokathexis, WHIM syndrome

Mutations in CXCR4 cause severe leukopenia in myelokathexis or WHIM syndrome. Plerixafor inhibits binding of CXCR4 to its ligand CXCL12. We investigated the effects of plerixafor (0.04 to 0.24 mg/kg) administered at 2-4 day intervals in 6 patients. Outcome measures were the patients' complete blood cell counts, CD34+ cell counts and lymphocyte subtypes compared with 5 normal subjects similarly treated with plerixafor. All patients showed prompt leukocytosis with maximum blood neutrophils and lymphocytes at 6-12 hours. Blood neutrophils peaked at 6-12 hours, increasing from a mean baseline of 0.4 ± 0.1 × 109/L, to mean peak of 4.5 ± 0.78 × 109/L. Lymphocytes also increased; the greatest increase was in B cells (CD19+ cells), a > 40-fold increase over baseline at the 0.08 mg/kg dose. None of the patients experienced any significant adverse effects. Plerixafor is a promising therapy for this condition.